| Stereochemistry | ACHIRAL |
| Molecular Formula | C16H17FIN3O4 |
| Molecular Weight | 461.2268 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1C(=O)C(C)=CC(C(=O)NOCCO)=C1NC2=CC=C(I)C=C2F
InChI
InChIKey=RWEVIPRMPFNTLO-UHFFFAOYSA-N
InChI=1S/C16H17FIN3O4/c1-9-7-11(15(23)20-25-6-5-22)14(21(2)16(9)24)19-13-4-3-10(18)8-12(13)17/h3-4,7-8,19,22H,5-6H2,1-2H3,(H,20,23)
| Molecular Formula | C16H17FIN3O4 |
| Molecular Weight | 461.2268 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
AZD-8330 is a potent, selective, orally active MEK inhibitor that blocks signal transduction pathways implicated in cancer cell proliferation and survival. AZD-8330 has shown tumor suppressive activity in multiple preclinical models of human cancer including melanoma, pancreatic, colon, lung, and breast cancers. AZD-8330 specifically inhibits mitogen-activated protein kinase kinase 1 (MEK or MAP/ERK kinase1), resulting in inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK is a key component of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth; constitutive activation of this pathway has been implicated in many cancers. AZD-8330 had been in phase I clinical trials by AstraZeneca for the treatment of malignancies. However, this research has been discontinued.
CNS Activity
Originator
Approval Year
Cmax
AUC
Sourcing
PubMed
Sample Use Guides
Patients with refractory cancer or cancer with no standard therapy received either once-daily (OD) or twice-daily (BID) oral AZD-8330 on day 1 followed by a 7-day washout period and continuous dosing from day 8. The starting dose was 0.5 mg with dose escalations in subsequent cohorts until a non-tolerated dose was reached. The MTD was defined as 20mg BID.
Route of Administration:
Oral
AZD-8330 potently and strongly inhibits MEK 1/2. AZD-8330 has no inhibitory activity against over 200 other kinases including at concentrations up to 10 uM. AZD-8330 demonstrates sub-nanomolar potency in mechanistic (pERK) and low to sub-nanomolar potency in functional (proliferation) assays in MEK 1/2 inhibitor sensitive cell lines.
